OVERALL DESCRIPTION This is a multidisciplinary investigation of mechanisms underlying the adverse health effects of exposure to complex mixtures of carcinogenic metals and polycyclic aromatic hydrocarbons (PAHs), and the development of effective strategies for bioremediation of PAHs in metal-contaminated mixtures. The four biomedical research projects address the mechanisms of toxicity and mutagenicity of carcinogenic metals and their impact on PAH metabolism and mutagenicity. Two projects will make use of assay systems in yeast, mammalian cell, and transgenic mouse to elucidate the mutagenicity of chromium and arsenic, and their impact on the mutagenicity of PAHs. One project is focused on determining the effect of chromium and arsenic on Ah receptor-dependent PAH metabolism. One project will investigate the impact of arsenic on signal transduction events in human skin melanocytes and karatinocytes. The ultimate goal of this biomedical research is to improve risk assessment through a more complete understanding of underlying mechanisms of toxicity and mutagenicity. The four non-biomedical research projects focus on the development of strategies for the biodegradation of PAHs and on the impact of metals on the viability and degradative capacity of microbial populations. Another project will assess the degradative capacity of microorganisms in soil biofilms. One project will focuse on a characterization of degradative microbial populations and the genetics underlying their biodegradation capacity and responses to metals. One project will investigate the influence of the rhizosphere on microbial communities and their degradative capacity. One project will focuse on the biochemistry and genetics of PAH biodegradation in complex mixtures of PAHs or PAHs and metals. The ultimate goal of this non-biomedical research is the development of effective and efficient bioremediation strategies. The Analytical Core and the Biostatistics Core provide essential services and methods development for the projects, leading to a more integrated approach. Other program goals are to provide a link between the program and local and regional environmental health professionals and science/health education professionals, and to provide an interdisciplinary training program for Ph.D. students and postdoctoral assistants in environmental health sciences. The long term goal is to promote collaborative efforts aimed at applying the new mechanistic information on potential health effects of complex mixtures to the development and evaluation of bioremediation strategies which will ultimately lead to risk reduction.